Monday, August 07, 2006

Sane Geneticists probably don't have Teleporters

Today's Narbonic is wonderful. I mean, what's the point of being sane if I can't have my teleporter?

(This is an awesome webcomic that you should read, and will enjoy even if you aren't a slightly unhinged geneticist wondering when her cloning will finally come right and data will start coming in.)

In other news, I am wondering when my cloning will finally come right and data will start coming in. I mean, I understand that one of the few things bacteria are really good at is recombination, but I've been working at cloning this one vector for a good two months with no success whatsoever. I'm way past the third-time's-the-charm rule for ligations, and that appears to be the problem with the last one; the insert just doesn't want to pop in. I know, I've been told a million and one times that the first few months you work in a new lab are never good, even when you're a post doc who knows the procedures like the back of her hand, not to mention being a student fairly well-versed in PCR and gel electrophoresis, and the cutting up of mouse embryos, and perhaps some staining, but without much experience in the land of cloning. Well, I'm getting that.

So during incubations, while randomly surfing the net for something that had enough text I wouldn't feel guilty for reading lots of webcomics at work, I found this. Go ahead and read it, I recommend it as not as puerile and offensive as many articles of its ilk. It tries to be scientific and not necessarily in a bad way. But there's still something wrong, some nagging itch at the back of my mind. The basic point of the article is as follows: 1) Humans and apes are not as similar as previously thought, which implies 2) that humans were, after all, created by God in his image. I know I'm not doing it justice, you should read the article if you want to know the actual argument. I'll just include quotes.

"While many evolutionists proclaim that human DNA is 98% identical to chimpanzee DNA, few would lie by idly and allow themselves to receive a transplant using chimpanzee organs. As a matter of fact, American doctors tried using chimp organs in the 1960s, but in all cases the organs were totally unsuitable."

My problem with the term 'evolutionists' notwithstanding, this argument is as misleading as the statement that "Human DNA is 98% identical to chimpanzee DNA." Most human organs are completely unsuitable for transplantation into other humans -- finding a suitable donor isn't just a matter of matching blood types and going. Immune response to foreign (although still perfectly human) organs and rejection of them is an incredibly serious issue in medicine, which spurs some of the research into stem cells and artificial tissue growth -- the only way to be sure that someone's body won't reject the organ is to regrow an organ from that same person's tissue. Which highlights the fact that "totally unsuitable" in this case might or might not mean functionally different, structurally different, or wracked with differences similar to those between individual humans. As a matter of fact, human hearts and even mouse hearts look very similar (although obviously of different sizes) and function almost identically. The fact that chimp organs cannot be transplanted means next to nothing.

However, after that rocky start, the article goes into even rougher territory when it begins to take issue with the concept that genetic similarity between humans and chimps does exist. Here are some highlights:

"It appears that only about 1.5% of the human genome consists of genes, which code for proteins. These genes are clustered in small regions that contain sizable amounts of “non-coding” DNA (frequently referred to as “junk DNA”) between the clusters. The function of these non-coding regions is only now being determined. These findings indicate that even if all of the human genes were different from those of a chimpanzee, the DNA still could be 98.5 percent similar if the “junk” DNA of humans and chimpanzees were identical. "

This argument just smacks of poor logic. First of all, the pre-genomic sequence homology study was done entirely on a selection of known genes; that was the only way they could do the study. The study (referenced earlier in this article) reported “that the average human polypeptide is more than 99 percent identical to its chimpanzee counterpart” (King and Wilson, 1975, pp. 114-115). A polypeptide is certainly not coded for by junk DNA, as the author of apologetics press's article obviously knew. So we know, and the author knows, that the 98.5% homology, whether true or false, is certainly not accounted for by homology in junk DNA. This argument, then, is purposely misleading. Worse than simply getting the numbers wrong, as an argument of whether humans and chimps are 98% similar, 95% similar, or 80% similar would be -- the author appears here to conciously misrepresent findings he referred to earlier in his article.

Here's another quote they use to back up a claim that DNA similarity isn't all that surprising:

"Because DNA is a linear array of those four bases—A,G,C, and T—only four possibilities exist at any specific point in a DNA sequence. The laws of chance tell us that two random sequences from species that have no ancestry in common will match at about one in every four sites. Thus even two unrelated DNA sequences will be 25 percent identical, not 0 percent identical (Marks, J. 2000, p. B-7)."

This is again entirely misleading. Even though an entirely unrelated sequence would in fact be 25% homologous, homology on the level of 95% for long peptides is still huge. Take a series of 30 bases; what would be required to code 10 amino acids in a protein (hardly anything on the scale of peptides which are at least 30 amino acids in length and usually in the realm of hundreds). In 30 bases, 95% homology means one, maybe two mismatches, as opposed to the seven or eight matches one would expect randomly. The chance that, even in a random population of 100 of these 30-base pair sequences, you would see a sinificant chunk at 95% homology is ridiculously small. Since the difference between the average homologies (25% and 95%) is 40%, in order to get a statistically insignificant result (p-value of 0.05 or higher) you would need a standard deviation between 20 and 30, which is impossible to have with a mean of 95 out of 100 (it would imply some greater than 100% homologies). This is assuming that the researchers aligned only about 100 sequences, which also is probably very false. So the fact that yes, a random sequence will probably be 25% homologous does not mean that the finding that most sequences are around 95% homologous is insignificant in the least. Remember, the original finding is that the average human polypeptide is 99 percent identical with a chimp polypeptide -- not that the total sequence is x% similar.

What I love the most is where this article goes next:

"Therefore a human and any earthly DNA-based life form must be at least 25% identical. Would it be correct, then, to state that daffodils are “one-quarter human”? The idea that a flower is one-quarter human is neither profound nor enlightening; it is outlandishly ridiculous!"

This argument just sets my teeth grinding in my mouth. First of all, it is more likely for "any earthly DNA-based life form" to be 0% identical with humans as it is for it to be 50% identical with humans if you espouse the idea that these similarities are purely random, so the statement that any life-form "must be at least 25% identical" is blatantly false and shows a disgusting lack of knowledge of statistical probability. I could go into that, but it's probably best that I don't. Secondly, in all probability, humans share a lot more than 25% of their DNA with daffodils. While E. Coli is probably a better example of what this author wanted to choose -- something arguably entirely unrelated to humans -- certain incredibly essential proteins, such as Ribosomal proteins, tRNAs, polymerases, and so-called "house-keeping" genes are incredibly similar between E. Coli and humans, which very well might boost the homology level above 25%. And it is significant -- it supports the idea that we share distant ancestry not just with chimpanzees, who in the scheme of things look like us, use tools like us, and even have some sort of rudimentary language like us, but indeed even with things as alien and apparently different as a tiny prokaryote.

Here's another gem: "The truth is, if we consider the absolute amount of genetic material when comparing primates and humans, the 1-2% difference in DNA represents approximately 80 million different nucleotides (compared to the 3-4 billion nucleotides that make up the entire human genome). To help make this number understandable, consider the fact that if evolutionists had to pay you one penny for every nucleotide in that 1-2% difference between the human and the chimp, you would walk away with $800,000. Given those proportions, 1-2% does not appear so small, does it? "

First, using the same reasoning: if you were given one penny for every nucleotide which stayed the same between human and chimp, you would walk away with $39,200,000. Given those proportions, 800 thousand seems rather small, doesn't it?

I could use actual logic, but it doesn't seem worth it.

Now the author changes the subject slightly and talks about chromosomal organization: "It would make sense that, if humans and chimpanzees were genetically identical, then the manner in which they store DNA also would be similar."

You mean, like, chromosomes with centromeric heterochromatin (regions of inactive DNA at the center of the chromosome, full of short tandem repeats) and telomeric ends (regions of inactive DNA at the end of the chromosome to protect the genes within from degradation), organized in a nucleus with specific regions of activity/inactivity, packed around histones, with certain alterations on the histones that make the DNA more accessible to proteins and certain alterations that make the histones hold the DNA tighter and keep it away from proteins? Something like that? Oh, wait, that is shared not only between chimps and humans but also more distant species. As opposed to, say, bacterial DNA which is simply floating in the cytoplasm in a large loop attached to the cellular inner membrane, or viral DNA which is jammed into a protien coat and sometimes not even DNA at all but RNA instead? Similar DNA storage?

But no, the author is here talking about the number of chromosomes: "All cells that possess a nucleus contain a specific number of chromosomes. Common sense would seem to necessitate that organisms that share a common ancestry would possess the same number of chromosomes. However, chromosome numbers in living organisms vary from 308 in the black mulberry (Morus nigra) to six in animals such as the mosquito (Culex pipiens) or nematode worm (Caenorhabditis elegans) [see Sinnot, et al., 1958]. Additionally, complexity does not appear to affect the chromosomal number. The radiolaria (a simple protozoon) has over 800, while humans possess 46. Chimpanzees, on the other hand, have 48 chromosomes. A strict comparison of chromosome numbers would indicate that we are more closely related to the Chinese muntjac (a small deer found in Taiwan’s mountainous regions), which also has 46 chromosomes."

First of all, how would common sense seem to necessitate that organisms that share a common ancestry possess the same number of chromosomes? Oh, because "To remove even one chromosome would potentially remove the DNA codes for millions of vital body factors." True. But what about two chromosomes fusing? An example being a recombination event between homologous parts of nonhomologous chromosomes (such as the end repeats, maybe?) at some point in germ line generation. The repetitive elements would be partially removed, oh no, and we would be left with one germ line cell which doesn't mature because it is missing quite a bit of DNA and one germ line cell which has fewer chromosomes. It isn't common. It isn't very likely. But it's possible; and we're not talking about one person and one generation here -- we're talking about millions upon millions of germ line cells times just as many generations. With so many chances, what's not to say that this happened? Certainly, most apes will breed to give apes and humans will breed to give humans. But given an isolated population, and perhaps something to select for in that recombination, maybe a gene suddenly not being in the repressive environment of the telomere and overexpressing, allowing for more (or different) development in certain parts of the brain, etc... You can get somewhere. They're still not humans, but they're on the way.

However, the next part gets better. "Amazingly, the authors found that only 48.6% of the whole human genome matched chimpanzee nucleotide sequences. [Only 4.8% of the human Y chromosome could be matched to chimpanzee sequences.] This study compared the alignments of 77,461 chimpanzee sequences to human genomic sequences obtained from public databases."

Okay, remember all of that "junk", "non-coding" DNA they were talking about earlier? Where 98.5% of the human genome could be identical to chimps and still have no coding sequence involved? Well, here's the hitch: those genomic sequences include the junk DNA, regions that don't code for proteins and hence aren't really strictly conserved over time. Of course you have binding sites in there, little bits of conserved sequences amid general lenghts of spacing DNA and unconserved sequences, but you don't have long stretches of homology because there's no reason to have that homology. If anything, the fact that the figures vary so much, that less than half of the whole genome is homologous, but that actual coding sequences, changes in which would have concrete effects, are conserved over time to a much greater extent supports the fact that changes HAPPEN, and the ones that don't effect much stick around or go away depending on random chance, but the ones tht are helpful stay there and the ones that are harmful go away. It argues for evolution, not against it.

Much of the rest of the article goes on about similarities between the great apes that are missing in humans, pointing to a tighter link among the great apes and an increased distance from humans. However, all of these arguments simply fail to be persuasive. Why should I believe this is evidence that humans had special creation by God when I can simply account for this difference by an earlier divergence from the great apes?

Finally, a part of the article that I loved almost the most: "After studying tissues and blood samples from the great apes, and sixty humans from various ethnic groups, Muchmore and colleagues discovered that human cells are missing a particular form of sialic acid (a type of sugar) found in all other mammals (1998, 107[2]:187)."

Interestingly enough, the particular form of sialic acid referenced here is commonly hypoexpressed in the brain, indicating that it is not amenable to brain development. Also interestingly, sialic acid can be released from cells and travel through the bloodstream to be picked up by other cells. What does this mean? Less (or, perhaps, none) of this cell marker in humans could very will be helpful to the increase in brain development and intelligence -- sounds like something evolution would select for, right? Especially in humans, where tool-making and intelligence had, for a long time, a direct impact on how much food you had and thereby how many children you had. Conveniently enough, the mutation in a hydroxylase protein that accounts for the lack of this form of sialic acid occurred in between the split between chimps and humans but before the divergence between neanderthals and humans -- exactly the right place to be looking for the development of human intelligence.

On another note, an interesting coincidence is that this hydroxylase protein is still expressed in humans, still at a lower level in the brain, but is non-functional. Why would God make humans with an ineffective version of this gene, expressed in exactly the same places? To confuse scientists? Or maybe this enzyme and its expression is a relic from a distant past.

I'm sure that a simple literature search such as the single google search I did on "sialic acid" would return interesting results in response to many of the other arguments in this article. I don't really have the time or energy for it, but this kind of pseudo-science really just gets on my nerves. It's perfectly fine in my opinion to cling to an irrational view that we are special, that we were created in God's image. It's nice to think you're better than the bacteria in your belly or the dogs on the street or the monkeys in the zoo. It's nice to think that all the other miraculous organisms were created for us to rule over and use.

But I think that in many ways it is simpler, and more beautiful to think that we are similar, that we came from the same place. Of course I look at the evidence before me in fossil records, in DNA homology, in skeletal similarities and vestigial limbs (such as our tailbones), and I see evidence for a common ancestor and evolution. But even on a spiritual level, there is something incredibly powerful about the idea of a common ancestor for all life. It puts you firmly as part of the beauty of the world, instead of placing you outside as an observer and overseer. That human life is as beautiful and simple and natural as a flower sprouting from the ground is, in my mind, just as magical as the idea that the flower was made for us and we were made to be like God.